Ozone, the major oxidant pollutant in photochemical smog, causes toxic injury to nasal and pulmonary airways. The overall goal of Project 3 is to determine the nature and distribution of airway mucosal injury, adaptation and repair in the nasal passages of neonatal and infant monkeys episodically exposed to ozone. Intranasal distribution and severity of the ozone-induced lesions will be determined by image analysis and standard morphometric techniques. The ozone-induced nasal alterations will be compared to biochemical changes in intracellular and extracellular antioxidants present in the nasal mucosa and extracellular airway lining fluid, respectively. The identified, site-specific alterations in mucosal morphology and in regional tissue/fluid biochemistry caused by episodic ozone exposures will also be compared to computer-assisted estimates of intranasal, regional dosimetry of ozone. The site-specific comparisons throughout the nasal passages will be used to determine how tissue susceptibility and airflow-driven dosimetry contribute to the pathogenesis of nasal epithelial and subepithelial injury and remodeling caused by acute and chronic ozone exposures. The results of these studies will provide a better understanding of how episodic ozone exposure affects the growth and development of the nasal airways at the macroscopic, microscopic and molecular levels of analysis. Our premise is that the developing nasal mucosa in neonatal and infant monkeys is more susceptible to the toxic effects of ozone than is the fully developed nasal mucosa of adult monkeys. We hypothesize that this disparity in mucosal responses is due to differences between infant and adult animals in the regulation of intracellular and extracellular antioxidants in the nasal airways. Project 3 is also designed to test the hypothesis that the ozone-induced morphologic, biochemical, and molecular responses of the nasal mucosa are sentinels for ozone-induced alterations in the distal pulmonary airways. Furthermore, this project will test the hypothesis that the episodic nature of the environmental exposure to ozone alters the House Dust Mite Allergen (HDMA)-induced allergic rhinitis in infant monkeys by fundamentally altering postnatal development of the nasal airway mucosa. This project will have critical input into all other projects and is crucial to the overall success of the program. In turn, this project will rely heavily on projects 1,2 and 4 to accomplish the proposed research.